67-71 Urinary System. Regulation of Body Fluids. Acid-Base Balance

Excretion Functions of the Organism and Systems Accomplishing Them

Excretion is a vital function of the body that involves removing metabolic waste products, foreign chemicals, and excess substances. The kidneys play a primary role in this function, supported by other excretory systems, including:

• The Respiratory System: Removes carbon dioxide and some volatile substances.

• The Liver and Gastrointestinal Tract: Eliminates bile pigments, cholesterol, and some toxins.

• The Skin: Excretes water, salts, and urea through sweat glands.

The kidneys are crucial for homeostasis, performing the following functions:

1. Excretion of Metabolic Waste and Foreign Substances: This includes urea (from amino acid metabolism), creatinine (from muscle metabolism), uric acid (from nucleic acids), and drug metabolites​.

2. Regulation of Water and Electrolyte Balance: The kidneys adjust excretion rates to maintain homeostasis, responding to changes in sodium intake and extracellular fluid levels​.

3. Regulation of Arterial Pressure: By controlling sodium excretion, renin secretion, and influencing vascular resistance.

4. Regulation of Acid-Base Balance: Through excretion of hydrogen ions and bicarbonate reabsorption.

5. Secretion and Metabolism of Hormones: Such as erythropoietin, vitamin D activation, and renin-angiotensin system control.

6. Gluconeogenesis: Production of glucose during fasting periods.

The Kidneys – Functional Structure

Each kidney consists of about one million nephrons, which are the basic functional units responsible for urine formation​. The kidney structure includes:

• Cortex: Contains the majority of nephrons.

• Medulla: Organized into renal pyramids, with the loops of Henle and collecting ducts contributing to urine concentration.

• Renal Pelvis and Calyces: Collect urine before it drains into the ureter​.

Each nephron consists of:

1. Glomerulus: A capillary network where plasma filtration occurs.

2. Bowman’s Capsule: Surrounds the glomerulus and collects filtrate.

3. Proximal Tubule: Reabsorbs essential substances like glucose, amino acids, and ions.

4. Loop of Henle: Concentrates urine via a countercurrent mechanism.

5. Distal Tubule and Collecting Duct: Adjust final urine composition under hormonal control.

Peculiarities of the Kidneys’ Blood Supply

The kidneys receive about 22% of the cardiac output (1100 mL/min), ensuring efficient filtration​. The renal blood supply follows this pathway:

• Renal Artery → Interlobar Arteries → Arcuate Arteries → Interlobular Arteries → Afferent Arterioles → Glomerular Capillaries (Filtration Site) → Efferent Arterioles → Peritubular Capillaries → Renal Vein.

Unique Features of Kidney Blood Supply:

• Two Capillary Beds in Series: The glomerular capillaries (high pressure, ~60 mmHg, favoring filtration) and theSympathetic Nervous System: Regulates renal blood flow and sodium reabsorption. Sympathetic activation constricts afferent arterioles, reducing GFR and stimulating renin release​.

• Parasympathetic Innervation: Minimal effect on kidney function but regulates bladder control​capillaries (low pressure, ~13 mmHg, favoring reabsorption)​.

• Autoregulation of Blood Flow: Maintains stable glomerular filtration rate (GFR) between arterial pressures of 75–160 mmHg

Peculiarities of the Kidneys’ Innervation

• Sympathetic Nervous System: Regulates renal blood flow and sodium reabsorption. Sympathetic activation constricts afferent arterioles, reducing GFR and stimulating renin release​.

• Parasympathetic Innervation: Minimal effect on kidney function but regulates bladder control​

Mechanism and Control of Glomerular Filtration

Glomerular filtration occurs across the glomerular capillary membrane, consisting of:

1. Fenestrated Endothelium (perforated with small holes allowing filtration)

2. Basement Membrane (collagen and proteoglycans prevent protein filtration)

3. Podocytes with Slit Pores (control passage of molecules)​

Determinants of Filtration:

• Glomerular Hydrostatic Pressure (GHP) (~60 mmHg) – Increases filtration

• Bowman’s Capsule Hydrostatic Pressure (BCHP) (~18 mmHg) – Opposes filtration

• Glomerular Capillary Colloid Osmotic Pressure (GCOP) (~32 mmHg) – Opposes filtration

• Net Filtration Pressure (NFP): ~10 mmHg (favoring filtration)

Regulation Mechanisms:

1. Myogenic Mechanism: Arteriolar smooth muscle contraction in response to stretch, preventing excessive GFR changes​

2. Tubuloglomerular Feedback (Macula Densa Sensing): Low NaCl in the distal tubule dilates afferent arterioles and increases renin release, maintaining GFR​

3. Hormonal Control:

   • Renin-Angiotensin System: Angiotensin II constricts efferent arterioles, increasing GFR​

   • Atrial Natriuretic Peptide (ANP): Reduces sodium reabsorption, increasing GFR​

   • Sympathetic Stimulation: Decreases GFR via vasoconstriction​

Methods of Glomerular Function Assessment

Several clinical methods assess kidney function:

1. Renal Clearance Concept:

   • Clearance of a substance (Cs) is calculated as

     C_s = (U_s x V) / P_s

   • U_s​ = Urine concentration of the substance.

   • V = Urine flow rate.

   • P_s​ = Plasma concentration of the substance

2. Glomerular Filtration Rate (GFR) Measurement:

   • Inulin Clearance: The gold standard for GFR measurement since inulin is freely filtered but not reabsorbed or secreted​.

   • Creatinine Clearance: Commonly used but slightly overestimates GFR due to minor tubular secretion​.

3. Blood Urea Nitrogen (BUN) and Serum Creatinine:

   • Elevated levels indicate decreased GFR and impaired renal function.

4. Estimated GFR (eGFR) Equations:

   • Cockcroft-Gault Formula: Uses creatinine clearance and patient factors like age and weight.

   • Modification of Diet in Renal Disease (MDRD) Formula: More accurate in chronic kidney disease (CKD) patients.

Functions of Renal Tubules

The renal tubules play a crucial role in urine formation through reabsorption, secretion, and concentration of filtrate. The major segments of the nephron and their functions include:

1. Proximal Tubule:

   • Reabsorbs 65% of filtered sodium, chloride, and water​

   • Reabsorbs nearly all glucose, amino acids, and bicarbonate.

   • Secretes hydrogen ions, organic acids, and bases​.

   • Plays a key role in acid-base balance.

2. Loop of Henle:

   • Descending Limb: Highly permeable to water but not solutes, concentrating the filtrate.

   • Ascending Limb: Impermeable to water; actively reabsorbs sodium, potassium, and chloride, making the filtrate dilute​

3. Distal Tubule:

   • Reabsorbs sodium and chloride while being impermeable to water in the absence of ADH.

   • Secretes potassium and hydrogen ions​.

4. Collecting Duct:

   • Regulated by ADH, which controls water permeability.

   • Secretes hydrogen ions, contributing to acid-base regulation.

   • Reabsorbs urea, which plays a role in urine concentration

Transport Processes in Renal Tubules

Reabsorption and secretion occur through active and passive transport mechanisms:

• Active Transport:

  • Sodium is transported via Na+/K+ ATPase, creating an electrochemical gradient​.

  • Glucose and amino acids are reabsorbed via Na+-co-transporters.

• Passive Transport:

  • Water moves by osmosis through aquaporins, following sodium movement.

  • Chloride follows sodium through electrical gradients​.

  • Urea diffuses passively but is facilitated in the collecting duct by urea transporters​.

• Countercurrent Mechanism:

  • The loop of Henle establishes a concentration gradient to facilitate water reabsorption.

  • The vasa recta maintains osmotic balance, preventing washout of the medullary gradient​

Mechanisms for Excretion of a Dilute Urine

When water intake is high, the kidneys:

• Reduce ADH secretion, decreasing water permeability in the distal tubule and collecting duct.

• Continue active reabsorption of NaCl in the ascending loop of Henle and distal tubule.

• Produce urine as dilute as 50 mOsm/L (one-sixth the osmolarity of plasma)​.

Key processes:

1. Proximal Tubule: Reabsorbs solutes and water equally (isosmotic)

2. Loop of Henle: Water is not reabsorbed in the ascending limb, diluting the filtrate

3. Distal Tubule and Collecting Ducts: No ADH → no water reabsorption, resulting in large amounts of dilute urine

Mechanisms for Excretion of a Concentrated Urine

When water is scarce, the kidneys:

• Increase ADH secretion, enhancing water reabsorption in the collecting duct.

• Use the countercurrent multiplier system to concentrate urine up to 1200-1400 mOsm/L​.

Key processes:

1. Loop of Henle: Creates a hyperosmotic medulla (due to NaCl and urea reabsorption).

2. Distal Tubule & Collecting Duct:

   • ADH increases water permeability, allowing water to be reabsorbed into the hyperosmotic medulla.

   • Urea reabsorption in the medullary collecting duct helps maintain the concentration gradient​.

3. Vasa Recta: Preserves medullary hyperosmolarity by preventing solute washout​

Renal Excretion

Excretion depends on three processes:

1. Glomerular Filtration: Determines the amount of solutes and water entering the nephron.

2. Tubular Reabsorption: Adjusts fluid composition by reclaiming essential solutes (e.g., sodium, glucose).

3. Tubular Secretion: Removes additional waste products like H+, K+, creatinine, and drugs​.

Urinary Excretion Formula:

Excretion = Filtration − Reabsorption + Secretion

• Sodium and water balance: Adjusted through hormonal control (ADH, aldosterone).

• Acid-base balance: Managed through H+ secretion and bicarbonate reabsorption​.

• Nitrogenous waste removal: Urea and creatinine are poorly reabsorbed, ensuring their excretion​

Renal Clearance Tests

Renal clearance tests measure the ability of the kidneys to clear substances from the plasma, helping assess kidney function. The general formula for clearance (C_s​) is:

• Clearance of a substance (C_s) is calculated as

  C_s = (U_s x V) / P_s

• U_s​ = Urine concentration of the substance.

• V = Urine flow rate.

• P_s​ = Plasma concentration of the substance

Common Clearance Tests:

1. Inulin Clearance (Gold Standard for GFR Measurement)

   • Inulin is freely filtered but neither reabsorbed nor secreted.

   • GFR = Clearance of inulin ( 125ml/min~125 ml/min 125ml/min)​.

2. Creatinine Clearance

   • Endogenous marker of kidney function.

   • Slightly overestimates GFR due to minor tubular secretion.

   • GFR ≈ 90-140 ml/min in healthy adults​.

3. Para-Aminohippuric Acid (PAH) Clearance (Renal Plasma Flow)

   • PAH is actively secreted; ~90% is excreted in urine.

   • Effective renal plasma flow (ERPF) ≈ 650 ml/min​.

4. Blood Urea Nitrogen (BUN) & Serum Creatinine

   • Elevated in kidney dysfunction.

   • BUN:Creatinine Ratio can differentiate prerenal from renal causes.

Volume of Urine and Its Components

Urine Volume:

• Normal range: 800-2000 mL/day, depending on hydration and hormonal regulation.

Urine Composition:

• Water (~95%)

• Solutes (~5%):

  • Electrolytes: Na+, K+, Cl-, Ca2+, Mg2+, phosphate.

  • Nitrogenous Wastes: Urea, creatinine, uric acid​.

  • Organic Compounds: Urobilin (gives urine its yellow color), hormones, metabolites.

  • Abnormal Components: Glucose (diabetes), proteins (kidney damage), ketones (starvation/diabetes).

Micturition (Urination)

Micturition is a reflex process controlled by the nervous system and bladder musculature.

1. Bladder Filling:

   • Bladder capacity: 300-400 mL before significant pressure increase​.

   • Stretch receptors activate at ~150 mL, sending signals to the spinal cord​.

2. Micturition Reflex:

   • Parasympathetic nerves stimulate detrusor muscle contraction.

   • Simultaneously, internal urethral sphincter relaxes.

   • If conditions are appropriate, external urethral sphincter (voluntary) relaxes, allowing urination​.

3. Higher Brain Centers:

   • Brainstem (pons): Facilitates or inhibits reflex.

   • Cerebral cortex: Provides voluntary control​

4. Disorders:

   • Atonic Bladder: Loss of sensory input (e.g., spinal cord injury) → Overflow incontinence​.

   • Neurogenic Bladder: Uncontrolled contractions due to loss of inhibitory signals​

Endocrine and Metabolic Functions of the Kidneys

The kidneys act as endocrine organs, regulating several physiological processes.

1. Endocrine Functions:

   • Erythropoietin (EPO): Stimulates RBC production in response to hypoxia​.

   • Renin: Part of the Renin-Angiotensin-Aldosterone System (RAAS), regulating blood pressure and fluid balance.

   • Vitamin D Activation: Converts 25(OH)D to active 1,25(OH)₂D₃ (Calcitriol), enhancing calcium absorption​.

   • Atrial Natriuretic Peptide (ANP): Promotes sodium excretion, reducing blood volume​.

2. Metabolic Functions:

   • Gluconeogenesis: The kidneys synthesize glucose during prolonged fasting.

   • Acid-Base Balance: Regulate H+ secretion and bicarbonate reabsorption to maintain pH​

Control of Renal Functions

Renal function is tightly regulated by:

1. Autoregulation:

   • Myogenic response: Afferent arteriole constriction prevents excessive GFR changes.

   • Tubuloglomerular feedback: Macula densa senses NaCl, adjusting renin release​.

2. Hormonal Control:

   • RAAS: Angiotensin II constricts efferent arterioles, increasing GFR.

   • ADH (Vasopressin): Increases water reabsorption via aquaporins in the collecting ducts​.

   • Aldosterone: Enhances sodium reabsorption in the distal tubule.

3. Sympathetic Nervous System:

   • Reduces renal blood flow during stress (vasoconstriction)​

Water-Electrolyte Balance of the Organism

Water-electrolyte balance ensures homeostasis by regulating fluid volume and ionic composition. The major electrolytes involved include:

• Sodium (Na⁺): Main extracellular cation, regulates osmolarity and blood pressure.

• Potassium (K⁺): Main intracellular cation, critical for nerve conduction and muscle function.

• Chloride (Cl⁻): Major anion, balances osmolarity.

• Calcium (Ca²⁺): Essential for bones, neuromuscular function.

• Magnesium (Mg²⁺): Involved in enzymatic reactions.

• Phosphate (HPO₄²⁻): Important for ATP production and pH buffering.

Body Fluids and Electrolytes

The body fluid compartments include:

1. Intracellular Fluid (ICF): ~40% of body weight, high in K⁺, Mg²⁺, and phosphate.

2. Extracellular Fluid (ECF): ~20% of body weight, high in Na⁺, Cl⁻, and bicarbonate.

   • Interstitial Fluid: Surrounds cells.

   • Plasma: Intravascular fluid, maintains circulation.

   • Transcellular Fluid: Includes cerebrospinal fluid, synovial fluid, etc.

Osmolarity is maintained at ~300 mOsm/L to prevent excessive shifts between compartments.

Dynamics of Body Fluid Volume and Osmolality

Fluid movement is controlled by hydrostatic and osmotic pressures:

• Osmotic balance: Water moves from low to high osmolarity.

• Hydrostatic pressure: Pushes water out of capillaries.

• Oncotic pressure (plasma proteins): Pulls water into capillaries.

Fluid shifts occur in conditions like dehydration (hyperosmolarity) or overhydration (hypoosmolarity).

Control of Water-Salt Homeostasis

• Renin-Angiotensin-Aldosterone System (RAAS):

  • Renin release (from kidneys) → Angiotensin II → vasoconstriction & aldosterone secretion.

  • Aldosterone increases Na⁺ reabsorption, promoting water retention.

• Antidiuretic Hormone (ADH/Vasopressin):

  • Released in response to high plasma osmolarity.

  • Increases water reabsorption in the collecting ducts.

• Atrial Natriuretic Peptide (ANP):

  • Released from atria in response to high blood volume.

  • Inhibits Na⁺ reabsorption, promoting diuresis.

• Sympathetic Nervous System:

  • Constricts renal arterioles → reduces urine output.

Thirst – Physiological Mechanisms

Thirst is triggered by:

1. Increased Plasma Osmolarity (Detected by osmoreceptors in the hypothalamus).

2. Decreased Blood Volume/Pressure (Activates RAAS).

3. Dry Mouth & Throat (Sensory stimulation of thirst center).

Drinking fluids restores balance by diluting plasma and reducing osmoreceptor activity.

Acid-Base Balance of the Organism

The body maintains a pH range of 7.35–7.45 to ensure proper enzyme function and cellular activity. Three major systems regulate acid-base balance:

1. Buffer Systems: Immediate response.

2. Respiratory System: Rapid (minutes) regulation via CO₂ elimination.

3. Renal System: Slow (hours to days) but powerful regulation through H⁺ excretion and bicarbonate reabsorption.

Buffer Systems of Body Fluids

Buffer systems prevent drastic pH changes by absorbing or releasing hydrogen ions (H⁺).

1. Bicarbonate (HCO₃⁻)/Carbonic Acid (H₂CO₃) Buffer System:

   • Major extracellular buffer

     CO₂ + H₂O ←→ H₂CO₃ ←→ H⁺ + HCO₃^-

   • Lungs control CO₂, and kidneys regulate HCO₃⁻, maintaining pH.

2. Protein Buffer System:

   • Intracellular and plasma proteins (e.g., hemoglobin, albumin) bind or release H⁺.

3. Phosphate Buffer System:

   • Active in intracellular fluid and renal tubules:

     H₂PO₄^- ←→ H⁺ + HPO₄^2-

4. Ammonia (NH₃/NH₄⁺) Buffer System:

   • Important in renal tubules for acid excretion:

     NH₃ + H⁺ → NH₄⁺

Respiratory Regulation of pH

• CO₂ acts as an acid (via carbonic acid formation).

• Lungs regulate pH by controlling CO₂ levels:

  • Hyperventilation → ↓ CO₂ → Raises pH (Alkalosis).

  • Hypoventilation → ↑ CO₂ → Lowers pH (Acidosis).

• Respiratory compensation occurs within minutes.

Renal Regulation of pH

The kidneys regulate pH by:

1. HCO₃⁻ Reabsorption:

   • Proximal tubule reabsorbs ~85% of filtered HCO₃⁻.

2. H⁺ Secretion:

   • Active in distal tubule and collecting duct.

   • Excess H⁺ binds with phosphate (H₂PO₄⁻) or ammonia (NH₄⁺) for excretion.

3. New HCO₃⁻ Generation:

   • Occurs when excess acid is excreted, replenishing bicarbonate stores.

• Renal compensation takes hours to days but is highly effective.

Abnormalities in Acid-Base Balance

• Respiratory Acidosis (↓ pH, ↑ CO₂):

  • Causes: Hypoventilation, COPD, lung disease.

  • Compensation: Kidneys retain HCO₃⁻, excrete H⁺.

• Respiratory Alkalosis (↑ pH, ↓ CO₂):

  • Causes: Hyperventilation, anxiety, high altitude.

  • Compensation: Kidneys excrete HCO₃⁻.

• Metabolic Acidosis (↓ pH, ↓ HCO₃⁻):

  • Causes: Diabetic ketoacidosis, renal failure, diarrhea.

  • Compensation: Lungs increase ventilation (↓ CO₂).

• Metabolic Alkalosis (↑ pH, ↑ HCO₃⁻):

  • Causes: Vomiting, diuretics, excessive bicarbonate intake.

  • Compensation: Lungs reduce ventilation (↑ CO₂)